TVP23B

TVP23B is a trans-Golgi transmembrane protein that physically interacts with YIPF6 and is required for maintaining critical glycosylation enzymes within the Golgi proteome of colonocytes, thereby controlling Paneth cell homeostasis, goblet cell mucin glycosylation, and the formation of a sterile intestinal mucus barrier (PMID:37339972). Loss of TVP23B leads to decreased antimicrobial peptide production, a more penetrable mucus layer, and susceptibility to colitis (PMID:37339972).

1. 2023 High

   Forward genetics and proteomics established that TVP23B is a trans-Golgi protein that partners with YIPF6 to maintain Golgi glycosylation enzyme composition, thereby controlling Paneth cell function, goblet cell mucin glycosylation, and intestinal barrier integrity — answering how this previously uncharacterized transmembrane protein contributes to mucosal defense.

   Evidence ENU mutagenesis screen in mice, co-immunoprecipitation of TVP23B–YIPF6, Golgi proteomics of TVP23B/YIPF6-deficient colonocytes, in vivo mucus penetrability assays, and chemically/infectiously induced colitis models

   PMID:37339972

   Open questions at the time

   • The mechanism by which TVP23B–YIPF6 interaction retains or recruits specific glycosylation enzymes to the Golgi is undefined
   • Whether TVP23B has direct enzymatic or transporter activity versus acting as a structural scaffold is unknown
   • Relevance of TVP23B-dependent glycosylation outside the intestinal epithelium has not been explored
2. 2025 Medium

   Macrophage-specific silencing of Tvp23b after myocardial infarction improved cardiac function and reduced fibrosis, broadening TVP23B's biological role beyond intestinal epithelium to macrophage-mediated tissue remodeling.

   Evidence In vivo lipidoid nanoparticle-mediated silencing in macrophages in a mouse MI model, with spatial transcriptomics and macrophage secretome analysis (preprint)

   PMID:40894159

   Open questions at the time

   • Preprint; awaits peer review and independent replication
   • The molecular mechanism linking TVP23B to macrophage secretory programs that activate cardiac fibroblasts is not defined
   • Whether the cardiac fibrosis role depends on the same Golgi glycosylation pathway described in colonocytes is untested

• The direct molecular activity of TVP23B — whether it acts as a cargo receptor, structural scaffold, or has intrinsic enzymatic function — remains unknown, as does the structural basis of its interaction with YIPF6.
• No structural model of TVP23B or the TVP23B–YIPF6 complex exists
• No substrate or direct enzymatic activity has been assigned to TVP23B
• Tissue-specific and cell-type-specific functions beyond intestinal epithelium and macrophages are uncharacterized