The finding that overexpression of ALKAL2 could potentiate neuroblastoma progression in the absence of ALK mutation (Borenäs et al., 2021) echoes the relationship between ADCY3 and MC4R (Siljee et al., 2018), where a peripheral gene, ADCY3, can regulate/impair the function of a core gene, that is MC4R, within the energy-regulating melanocortin signaling pathway (Timshel et al., 2020). The gene discussed is ALKAL2; the disease is neuroblastoma.