Ceramide transfer protein (CERT) (CERT)

Ceramide transfer protein (CERT), encoded by the COL4A3BP gene, is a cytosolic protein that mediates the non-vesicular transport of ceramide from the endoplasmic reticulum (ER) to the Golgi apparatus [1][2]. This transport is facilitated by its C-terminal Steroidogenic Acute Regulatory protein-related Lipid Transfer (START) domain, which recognizes and extracts ceramide from the ER membrane [3]. Once at the Golgi, ceramide is utilized for the synthesis of sphingomyelin, a major component of plasma membranes and a regulator of cell signaling [2][4]. CERT is a recognized therapeutic target because its overexpression is linked to drug resistance and poor prognosis in various cancers, including breast and colorectal cancer [5]. Additionally, CERT is required for the replication of certain viruses and intracellular bacteria, such as the Hepatitis C virus and Chlamydia trachomatis [6]. Small-molecule inhibitors like HPA-12 target the START domain to block ceramide transport, thereby inducing ER stress and sensitizing cells to apoptosis [3][7]. Consequently, targeting the CERT START domain offers a potential strategy for overcoming chemoresistance and treating specific infectious diseases [5][7].

Other names

COL4A3BPCollagen type IV alpha-3-binding proteinGoodpasture antigen-binding proteinGPBPSTARD11StAR-related lipid transfer protein 11

Inhibition of ceramide transport from the endoplasmic reticulum to the Golgi apparatus by competitively binding to the hydrophobic pocket of the START domain.