GPBP or CERT: The Roles in Autoimmunity, Cancer or Neurodegenerative Disease-A Systematic Review

In 1999, Goodpasture antigen-binding protein (GPBP) was identified as a protein interacting with the N-terminal region of the human Goodpasture antigen, linked to collagen IV in patients with Goodpasture syndrome, an autoimmune disease. In 2003, a splice variant lacking a serine-rich domain was discovered, which is involved in the cytosolic transport of ceramide, leading to its renaming as Ceramide Transfer Protein (CERT). This dual functionality has sparked debate regarding the roles of GPBP/CERT, as they appear to participate in distinct research fields and are implicated in various pathologies. This review follows the guidelines of the Preferred Reporting Items for Systematic Reviews (PRISMA). It compiles data from searches on Medline (PubMed) and Web of Science conducted between February and November 2022. Out of 465 records, 47 publications were selected for review. The literature predominantly focuses on GPBP/CERT as ceramide transporters. Notably, no studies contradict either hypothesis, with substantial scientific evidence supporting both roles. The need for further research is clear, and new insights into these proteins' involvement in multiple pathologies could drive future therapeutic strategies. GPBP and CERT are multifunctional proteins with roles beyond collagen organization and ceramide transport, extending to autoimmune disorders, neurodegenerative diseases, and cancer. The ongoing controversy highlights the necessity for continued investigation, which promises to offer significant insights and potential therapeutic avenues.