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However, the molecular mechanisms that govern these maturational events are still poorly defined. Here we report that Clpsl2, a novel colipase homology, is exclusively expressed in the caupt epididymis and conserved in mammalian. Clpsl2 was secreted into the lumen and covered the acrosome region and principal piece of spermatozoa tail. And during epididymal transit, the binding rate between Clpsl2 protein and the spermatozoa gradually decreased. Though Clpsl2 had the highest identifies with pancreatic colipase (Clps), Clpsl2 lacked those conserved amino acids in pancreatic Clps that interacting with lipase, correspondingly, the recombinant Clpsl2 protein did not possess the Clps function such as promoting the hydrolysis of lipase to its substrate glycerine trioleate. However, sequence analysis showed that Clpsl2 has the potency to bind with lipid. Knockdown expression of <jats:italic>Clpsl2<\/jats:italic> by lentivirus\u2010mediated RNAi in vivo caused an attenuation of spermatozoa motility, a suppressed acrosomal reaction, a decrease of cauda spermatozoa number, and subfertility. This study identified a novel and conserved molecule, Clpsl2, was specifically expressed in epididymis and involved in the regulation of spermatozoa motility, acrosomal integrity, and male fertility.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.26668","type":"journal-article","created":{"date-parts":[[2018,1,11]],"date-time":"2018-01-11T16:54:34Z","timestamp":1515689674000},"page":"4760-4774","source":"Crossref","is-referenced-by-count":12,"title":["An epididymis\u2010specific secretory protein Clpsl2 critically regulates sperm motility, acrosomal integrity, and male fertility"],"prefix":"10.1002","volume":"119","author":[{"given":"Xiaosheng","family":"Lu","sequence":"first","affiliation":[{"name":"Key Laboratory for Regenerative Medicine (JNU\u2010CUHK), Ministry of Education, Department of Developmental and Regenerative Biology, College of Life Science and Technologies Jinan University Guangzhou P.R. 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