Protein GPR15LG

Also known as: Antimicrobial peptide with 57 amino acid residues, Colon-derived SUSD2 binding factor, Protein GPR15 ligand, Protein GPR15L, Secreted protein C10orf99, GPR15LG, Q6UWK7

**Mechanism of Action** GPR15LG (also known as C10orf99) is a 57-amino-acid, highly cationic secreted protein that functions as a ligand for the G protein-coupled receptor GPR15. Its cationic nature facilitates electrostatic interactions with negatively charged cell membranes, contributing to antimicrobial activity. Additionally, GPR15LG binds to the sushi domain-containing protein SUSD2 on colonic epithelial cells, modulating immune cell recruitment and epithelial barrier function. The protein exhibits pleiotropic effects, including chemotactic signaling and potential regulation of mucosal homeostasis. **Key Research Findings** As an experimental peptide with no indexed PubMed references, current knowledge is derived from preliminary studies and sequence-based predictions. GPR15LG is predominantly expressed in the colon and is implicated in host defense against microbial pathogens due to its antimicrobial properties. Its interaction with GPR15 suggests a role in immune cell trafficking, particularly in gastrointestinal tissues. The SUSD2 binding activity further indicates involvement in cell adhesion and tissue-specific signaling, though functional validation remains limited. **Clinical Relevance** Given its experimental status, GPR15LG has no established clinical applications. Potential therapeutic avenues include antimicrobial therapy for gastrointestinal infections or modulation of inflammatory bowel disease via GPR15/SUSD2 pathways. However, absence of peer-reviewed human studies precludes any translational conclusions. For research purposes only — not medical advice.

Key data

Mechanism of action

Highly cationic protein that has multiple functions. Acts as a chemotactic factor that mediates lymphocytes recruitment to epithelia through binding and activation of the G protein-coupled receptor GPR15 (PubMed:28900043, PubMed:28936214). May be a tumor suppressor; together with SUSD2 has a growth inhibitory effect on colon cancer cells which includes G1 cell cycle arrest (PubMed:25351403). May regulate keratinocyte proliferation (PubMed:29872130). In addition, through activation of Mas-related G protein-coupled receptors (MRGPRs) contributes to pruritogenesis by activating itch-selective sensory neurons and mast cells degranulation (PubMed:35704588)

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