diff --git a/biology/htslib/Makefile b/biology/htslib/Makefile
index 5a844cef433c..3d39f202a887 100644
--- a/biology/htslib/Makefile
+++ b/biology/htslib/Makefile
@@ -1,43 +1,42 @@
 PORTNAME=	htslib
-DISTVERSION=	1.17
-PORTREVISION=	1
+DISTVERSION=	1.21
 CATEGORIES=	biology devel
 # Github generated distfiles are incomplete, so use custom tarball
 MASTER_SITES=	https://github.com/samtools/htslib/releases/download/${DISTVERSION}/
 
 MAINTAINER=	jwb@FreeBSD.org
 COMMENT=	C library for high-throughput sequencing data formats
 WWW=		https://www.htslib.org/
 
 LICENSE=	BSD3CLAUSE MIT
 LICENSE_COMB=	multi
 LICENSE_FILE=	${WRKSRC}/LICENSE
 
 LIB_DEPENDS=	libdeflate.so:archivers/libdeflate
 TEST_DEPENDS=	bash:shells/bash
 
 USES=		autoreconf cpe gmake localbase pathfix perl5 shebangfix tar:bzip2
 USE_PERL5=	test
 USE_LDCONFIG=	yes
 
 GNU_CONFIGURE=		yes
 GNU_CONFIGURE_MANPREFIX=${PREFIX}/share
 MAKE_ARGS_armv6=	HTS_HAVE_NEON=
 MAKE_ARGS_armv7=	HTS_HAVE_NEON=
-MAKE_ARGS=		$(MAKE_ARGS_$(ARCH))
+MAKE_ARGS=		${MAKE_ARGS_${ARCH}}
 PATHFIX_MAKEFILEIN=	Makefile
 SHEBANG_FILES=		test/*.pl
 
 OPTIONS_DEFINE=		CURL
 OPTIONS_DEFAULT=	CURL
 
 CURL_DESC=		Use libcurl for network file access (HTTPS and S3 support).
 CURL_USES=		ssl
 CURL_LIB_DEPENDS=	libcurl.so:ftp/curl
 CURL_CONFIGURE_ENABLE=	libcurl
 
 PLIST_SUB=	PORTVERSION="${PORTVERSION}"
 
 TEST_TARGET=	test
 
 .include <bsd.port.mk>
diff --git a/biology/htslib/distinfo b/biology/htslib/distinfo
index 24c398cacc3c..f035bfd3f3d0 100644
--- a/biology/htslib/distinfo
+++ b/biology/htslib/distinfo
@@ -1,3 +1,3 @@
-TIMESTAMP = 1677245487
-SHA256 (htslib-1.17.tar.bz2) = 763779288c40f07646ec7ad98b96c378c739171d162ad98398868783b721839f
-SIZE (htslib-1.17.tar.bz2) = 4619884
+TIMESTAMP = 1727437235
+SHA256 (htslib-1.21.tar.bz2) = 84b510e735f4963641f26fd88c8abdee81ff4cb62168310ae716636aac0f1823
+SIZE (htslib-1.21.tar.bz2) = 4781943
diff --git a/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static32x16pr__neon.c b/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static32x16pr__neon.c
index 577a3d651321..434edf03f411 100644
--- a/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static32x16pr__neon.c
+++ b/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static32x16pr__neon.c
@@ -1,11 +1,11 @@
---- htscodecs/htscodecs/rANS_static32x16pr_neon.c.orig	2023-04-17 21:11:08 UTC
+--- htscodecs/htscodecs/rANS_static32x16pr_neon.c.orig	2024-10-09 21:43:35 UTC
 +++ htscodecs/htscodecs/rANS_static32x16pr_neon.c
 @@ -32,7 +32,7 @@
   */
  
  #include "config.h"
--#ifdef __ARM_NEON
-+#if defined(__ARM_NEON) && defined(__aarch64__)
+-#if defined(__ARM_NEON) && defined(__aarch64__)
++#if defined(__ARM_NEON)
  #include <arm_neon.h>
  
  #include <limits.h>
diff --git a/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static4x16pr.c b/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static4x16pr.c
index 8f3e883eec42..3eaebe7ae36d 100644
--- a/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static4x16pr.c
+++ b/biology/htslib/files/patch-htscodecs_htscodecs_rANS__static4x16pr.c
@@ -1,11 +1,11 @@
---- htscodecs/htscodecs/rANS_static4x16pr.c.orig	2023-04-17 21:13:50 UTC
+--- htscodecs/htscodecs/rANS_static4x16pr.c.orig	2024-10-09 21:44:38 UTC
 +++ htscodecs/htscodecs/rANS_static4x16pr.c
-@@ -1006,7 +1006,7 @@ unsigned char *(*rans_dec_func(int do_simd, int order)
+@@ -1030,7 +1030,7 @@ unsigned char *(*rans_dec_func(int do_simd, int order)
      }
  }
  
--#elif defined(__ARM_NEON)
-+#elif defined(__ARM_NEON) && defined(__aarch64__)
+-#elif defined(__ARM_NEON) && defined(__aarch64__)
++#elif defined(__ARM_NEON)
  
  #if defined(__linux__) || defined(__FreeBSD__)
  #include <sys/auxv.h>
diff --git a/biology/htslib/pkg-plist b/biology/htslib/pkg-plist
index 8c97aa84399c..1d4e538f1e47 100644
--- a/biology/htslib/pkg-plist
+++ b/biology/htslib/pkg-plist
@@ -1,43 +1,45 @@
+bin/annot-tsv
 bin/bgzip
 bin/htsfile
 bin/tabix
 include/htslib/bgzf.h
 include/htslib/cram.h
 include/htslib/faidx.h
 include/htslib/hfile.h
 include/htslib/hts.h
 include/htslib/hts_defs.h
 include/htslib/hts_endian.h
 include/htslib/hts_expr.h
 include/htslib/hts_log.h
 include/htslib/hts_os.h
 include/htslib/kbitset.h
 include/htslib/kfunc.h
 include/htslib/khash.h
 include/htslib/khash_str2int.h
 include/htslib/klist.h
 include/htslib/knetfile.h
 include/htslib/kroundup.h
 include/htslib/kseq.h
 include/htslib/ksort.h
 include/htslib/kstring.h
 include/htslib/regidx.h
 include/htslib/sam.h
 include/htslib/synced_bcf_reader.h
 include/htslib/tbx.h
 include/htslib/thread_pool.h
 include/htslib/vcf.h
 include/htslib/vcf_sweep.h
 include/htslib/vcfutils.h
 lib/libhts.a
 lib/libhts.so
 lib/libhts.so.%%PORTVERSION%%
 lib/libhts.so.3
 libdata/pkgconfig/htslib.pc
+share/man/man1/annot-tsv.1.gz
 share/man/man1/bgzip.1.gz
 share/man/man1/htsfile.1.gz
 share/man/man1/tabix.1.gz
 share/man/man5/faidx.5.gz
 share/man/man5/sam.5.gz
 share/man/man5/vcf.5.gz
 share/man/man7/htslib-s3-plugin.7.gz