FSIP2 (fibrous sheath interacting protein 2) is essential for sperm flagellar structure and function, with emerging roles in acrosome biogenesis. Located in the sperm fibrous sheath, midpiece, and principal piece, FSIP2 coordinates axonemal assembly and flagellar organization 1. Beyond its structural role, FSIP2 regulates acrosomal protein expression through interaction with proteins including DPY19L2, SPACA1, and HSP90B1, and influences mitochondrial sheath morphology and ATP consumption during spermatogenesis 2. FSIP2 may also function as an intra-flagellar transporter affecting mitochondrial selection 3. Biallelic FSIP2 mutations cause spermatogenic failure 34, manifesting as multiple morphological abnormalities of sperm flagella (MMAF) and asthenoteratozoospermia, characterized by flagellar disassembly, acrosomal hypoplasia, and abnormal mitochondrial sheath extension 23. FSIP2 variants are identified in male infertility cohorts through exome sequencing 45. Clinically, FSIP2-associated infertility responds favorably to assisted reproductive technologies, with intracytoplasmic sperm injection (ICSI) enabling successful pregnancies and live births 36, indicating that FSIP2 mutations cause functional rather than absolute infertility.