Kisspeptin-54: Full-Length KISS1 Isoform Research Guide

Kisspeptin-54 is the full-length 54-amino-acid KISS1 gene product and the longest naturally occurring kisspeptin isoform. Researchers use it to directly activate KISS1R on hypothalamic GnRH neurons, stimulate pulsatile GnRH secretion, and study HPG axis regulation with a pharmacokinetic profile distinct from the shorter kisspeptin-10 fragment.

Kisspeptin-54 (also designated metastin-54 or KP-54) is the 54-amino-acid C-terminal fragment of the KISS1 gene product — the longest naturally occurring isoform of the kisspeptin peptide family. Unlike the truncated kisspeptin-10 fragment (a 10-amino-acid C-terminal decapeptide cleaved from the same precursor by tissue kallikrein and related endopeptidases), kisspeptin-54 retains the complete sequence of the KISS1 protein's bioactive region. Both isoforms share the critical C-terminal RF-amide decapeptide sequence that engages the kisspeptin receptor (KISS1R, also termed GPR54) — a Gq/11-protein-coupled GPCR expressed predominantly on hypothalamic GnRH neurons in the arcuate and anteroventral periventricular nuclei. KISS1R activation by kisspeptin-54 triggers the canonical Gq/11 signaling cascade: receptor-coupled Gαq activates phospholipase C-β (PLCβ), hydrolyzing membrane phosphatidylinositol-4,5-bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3-me