CATSPERE encodes catsper channel auxiliary subunit epsilon, a critical auxiliary component of the CatSper ion channel complex essential for sperm function 1. In spermatozoa, CATSPERE localizes to the flagellum in quadrilateral nanodomains and is required for proper CatSper channel assembly and calcium ion influx 1. The protein functions in sperm hyperactivation and rheotactic efficiency—the ability to orient against fluid flow—which is necessary for successful sperm migration through the female reproductive tract and fertilization 1. Loss-of-function mutations in CATSPERE result in severe male subfertility; a homozygous in-frame 6-bp deletion (c.2393_2398delCTATGG) in exon 18 caused complete loss of CatSper function and fertilization failure in an infertile patient 2. Beyond reproductive function, CATSPERE has unexpected roles in colorectal cancer biology. A genome-wide association study identified a protective genetic variant (rs505706 A>G) upstream of CATSPERE associated with reduced colorectal cancer risk 3. CATSPERE upregulation promotes calcium-dependent apoptosis in colorectal cancer cells and inhibits tumor growth, suggesting calcium-signaling mechanisms may be shared between sperm physiology and cancer suppression 3.