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. Here, RPS6KA3 is linked to hypertriglyceridemia.