Reports of severe hypertriglyceridemia in infancy (Tan et al., 2023), recurrent severe hypercalcemia with nephrocalcinosis linked to a splice-site variant (Tise et al., 2022), central precocious puberty responsive to GnRH agonists (Song et al., 2022), and type 2 diabetes in adulthood within large kindred (Boulos et al., 2021) suggest intersecting disturbances of bone, energy, and endocrine signaling downstream of RSK2. This evidence concerns the gene GNRH1 and precocious puberty.