Chemokines are secreted proteins that promote a cell migration response during immune cell stimulation or development of the lymphoid tissue. In contrast, the functions of transmembrane-type chemokine-like factor (CKLF) and the protein family CMTM (CKLF-like MARVEL transmembrane domain-containing) are enigmatic. CKLF and CMTM1–CMTM8 are organized in gene clusters, and CMTM1 and CMTM2 show a testis-specific expression. In order to shed light on the physiological role of these proteins, Masahito Ikawa and colleagues (Fujihara et al., 2018) established mutant mouse lines for Cmtm1, Cmtm2a and Cmtm2b through CRISPR/Cas-9 gene editing. The authors find that male mice lacking Cmtm1 are fertile, but double mutants for Cmtm2a and Cmtm2b display fertility defects including having spermatozoa that are immobile and with a reduced zona pellucida (ZP)-binding ability. In addition, CMTM2A and CMTM2B might be part of a group proteins that are involved in the regulation of the sperm membrane protein ADAM3, which promotes sperm migration and ZP binding. Taken together, this study identifies a new role for transmembrane-type CKLFs in sperm biogenesis and opens the door for future research on the mechanisms of CMTM family proteins in fertility.