The molecular identity of the TLQP-21 peptide receptor

Bhavani S. Sahu, Megin E. Nguyen, Pedro Rodriguez, Jean Pierre Pallais, Vinayak Ghosh, Maria Razzoli, Yuk Y. Sham, Stephen R. Salton, Alessandro Bartolomucci

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations


The TLQP-21 neuropeptide has been implicated in functions as diverse as lipolysis, neurodegeneration and metabolism, thus suggesting an important role in several human diseases. Three binding targets have been proposed for TLQP-21: C3aR1, gC1qR and HSPA8. The aim of this review is to critically evaluate the molecular identity of the TLQP-21 receptor and the proposed multi-receptor mechanism of action. Several studies confirm a critical role for C3aR1 in TLQP-21 biological activity and a largely conserved mode of binding, receptor activation and signaling with C3a, its first-identified endogenous ligand. Conversely, data supporting a role of gC1qR and HSPA8 in TLQP-21 activity remain limited, with no signal transduction pathways being described. Overall, C3aR1 is the only receptor for which a necessary and sufficient role in TLQP-21 activity has been confirmed thus far. This conclusion calls into question the validity of a multi-receptor mechanism of action for TLQP-21 and should inform future studies.

Original languageEnglish
Pages (from-to)7133-7144
Number of pages12
JournalCellular and Molecular Life Sciences
Issue number23
StatePublished - Dec 2021


  • Adipocytes
  • C3a
  • C3aR1
  • Complement
  • G-protein-coupled receptor
  • HSPA8
  • Microglia
  • TLQP-21
  • VGF
  • gC1QR


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