CLPSL2 (colipase-like 2) is an epididymis-enriched gene that encodes a protein with enzyme activator activity and protein binding capacity 1. While CLPSL2 is abundantly expressed in the caput and corpus regions of the epididymis, CRISPR/Cas9-mediated knockout studies in mice demonstrate that it is not essential for male fertility or sperm function, as knockout males produced offspring at rates comparable to wild-type controls 1. However, genetic association studies in pigs suggest CLPSL2 involvement in male fertility traits, where the gene is strongly linked to SPDEF (r²=0.848) and implicated in susceptibility to respiratory disease through pleiotropic effects during selective breeding for reproductive traits 2. Computational prediction models have identified CLPSL2 as a candidate protein associated with breast cancer immunotherapy 3. Overall, CLPSL2 appears to function in reproductive physiology, though its precise molecular mechanisms and clinical significance remain incompletely characterized. The apparent redundancy in knockout studies contrasts with genetic association data, suggesting compensatory mechanisms or context-dependent functional importance.