Kisspeptins are ligands for the G protein-coupled receptor KISS1R/GPR54 (PubMed:11385580, PubMed:11457843, PubMed:11527393, PubMed:12879005, PubMed:15020672, PubMed:15596153). The hypothalamic KISS1/KISS1R signaling system plays a central role in the regulation of the hypothalamic-pituitary-gonadal reproductive axis by modulating the secretion of gonadotropin-releasing hormone (GnRH) from GnRH neurons (PubMed:15219839, PubMed:15598687, PubMed:22335740). In these neurons, kisspeptin binding to its receptor activates G(q)-dependent signaling, leading to phospholipase C (PLC) activation, and hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) (PubMed:15598687, PubMed:22335740). The subsequent rise in intracellular calcium levels results in the inhibition of inward rectifier potassium channels and activation of TRPC-like cation channels, leading to GnRH neurons depolarization and stimulation (By similarity). In addition to this pathway, kisspeptin also triggers G(q)-independent signaling via beta- arrestin, leading to MAPK cascade activation and ERK1/ERK2 phosphorylation (PubMed:25147978). Kisspeptins are also involved in the regulation of other processes including cell growth, cell proliferation and cell migration (PubMed:11385580, PubMed:11457843, PubMed:11527393, PubMed:12879005, PubMed:15020672, PubMed:15596153). {ECO:0000250|UniProtKB:Q6Y4S4, ECO:0000269|PubMed:11385580, ECO:0000269|PubMed:11457843, ECO:0000269|PubMed:11527393, ECO:0000269|PubMed:12879005, ECO:0000269|PubMed:15020672, ECO:0000269|PubMed:15219839, ECO:0000269|PubMed:15596153, ECO:0000269|PubMed:15598687, ECO:0000269|PubMed:22335740, ECO:0000269|PubMed:25147978}. [Kisspeptin-10]: Binds the G protein-coupled receptor KISS1R/GPR54 and triggers G protein-coupled receptor signaling via activation of G(q) and phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis by phospholipase C (PubMed:11457843, PubMed:22335740). Binding to the receptor also activates beta-arrestin-dependent signaling resulting in ERK1/2 phosphorylation (PubMed:11457843, PubMed:25147978). Activation of the receptor inhibits cell proliferation and cell migration, and is involved in the regulation of trophoblast invasion during early stages of pregnancy. Is also involved in the modulation of airway smooth muscle cells migration (PubMed:11457843, PubMed:15020672, PubMed:38512807). In bone tissue, activation of KISS1R by kisspeptin-10 recruits phosphatase DUSP18 and SRC to the KISS1R C-terminus through a G(q)-dependent signaling pathway. This leads to DUSP18-mediated dephosphorylation of SRC, down- regulation of osteoclast differentiation and activity, and consequently suppression of bone resorption (By similarity). {ECO:0000250|UniProtKB:Q6Y4S4, ECO:0000269|PubMed:11457843, ECO:0000269|PubMed:15020672, ECO:0000269|PubMed:22335740, ECO:0000269|PubMed:25147978, ECO:0000269|PubMed:38512807}. [Metastin]: Receptor binding triggers G protein-coupled receptor signaling via activation of G(q) and phosphatidylinositol 4,5- bisphosphate (PIP2) hydrolysis by phospholipase C. . This is the function of ENSG00000170498 (KISS1, KiSS-1 metastasis suppressor).