SUN5 (Sad1 and UNC84 domain containing 5) is a testis-specific nuclear envelope protein essential for male fertility that functions as a critical structural component of the sperm head-tail coupling apparatus (HTCA) 1. SUN5 anchors the sperm head to the tail by connecting the nuclear envelope to the cytoskeletal machinery 2. Mechanistically, SUN5 interacts with nuclear membrane protein LaminB1 to connect the nucleus and with cytoskeletal GTPase Septin12 to connect the proximal centriole, forming an LaminB1/SUN5/Septin12 complex that bridges the head-tail junction 1. SUN5 also cooperates with CENTLEIN and PMFBP1 as functional partners within the HTCA 3. Disease-relevant mutations in SUN5 represent the most frequent genetic cause (33-47%) of acephalic spermatozoa syndrome (ASS), a severe male infertility condition characterized by sperm decapitation 1. SUN5 mutations impair protein folding, cellular localization, and interactions with binding partners like DNAJB13, disrupting head-tail integrity 2. Clinically, SUN5 deficiency causes complete male sterility due to production of acephalic spermatozoa, though intracytoplasmic sperm injection (ICSI) can overcome this defect 4. Recent reports identify novel SUN5 variants associated with oligoasthenoteratozoospermia, expanding the mutational spectrum of male infertility 5.