ODF2 encodes a major structural protein component of the outer dense fibers (ODFs) in mammalian sperm tails, which are filamentous structures located outside the axoneme in the midpiece and principal piece regions 1. The protein functions as a cytoskeletal component required for flagellar beating and stability during sperm transport 2. ODF2 interacts specifically with ODF1 through leucine zipper-mediated interactions during ODF assembly along the sperm axoneme 1. Haploinsufficiency of ODF2 causes a distinct form of decapitated and decaudated spermatozoa (DDS) characterized by sperm neck-midpiece separation, leading to the formation of immotile headneck sperm cells and motile but directionless neckless tails 2. Reduced ODF2 expression is associated with decreased sperm motility in asthenospermia patients, with both mRNA and protein levels significantly decreased in moderate to severe cases 3. The protein is regulated post-transcriptionally by microRNA-23a/b-3p, and its downregulation correlates with oligoasthenozoospermia 4. ODF2 serves as a fertility biomarker in breeding bulls, with high protein levels correlating with superior fertility outcomes 5. Age-related studies show ODF2 expression peaks in late adult males but declines with advanced age, potentially contributing to age-associated fertility decline 6.