CKLF-like MARVEL transmembrane domain-containing protein 4 (CMTM4)

CKLF-like MARVEL transmembrane domain-containing protein 4 (CMTM4) is a tetra-transmembrane protein and member of the chemokine-like factor family, encoded on chromosome 16q21-q22.1[3][5]. It functions as a context-dependent protein involved in tumor progression, immune regulation, and cell cycle control[6]. CMTM4 is a component of the IL-17 receptor complex, essential for IL-17RC glycosylation and surface trafficking, thereby regulating IL-17A/F signaling[2][3]. It also supports PD-L1 stability on the cell membrane, acting redundantly with or as a backup for CMTM6, and thereby plays a role in immune checkpoint regulation and tumor immune evasion[1][5][6]. CMTM4 frequently acts as a tumor suppressor, with reduced expression linked to increased incidence or poor prognosis in several cancers, including colorectal cancer, clear cell renal carcinoma, and certain brain tumors[3][4][6]. Overexpression can arrest the cell cycle at G2/M by upregulating p21, independently of apoptosis[4]. This makes CMTM4 both a marker and a potential therapeutic target for cancer and immune-related conditions, although there are currently no known drugs that directly target it[5][6].

Other names

CKLFSF4Chemokine-like factor superfamily member 4Chemokine-like factor super family 4Chemokine-like factor superfamily 4

Regulates stability and plasma membrane expression of PD-L1/CD274 via inhibition of polyubiquitination. Required for IL-17RC glycosylation and surface expression as a subunit of the IL-17 receptor complex. Induces cell cycle arrest via p21 upregulation.