Indeed, the defective function of an increasing number of proteins (i.e., neurofibromin, LZTR1, SPRED1 and SPRED2) provides evidence of multiple circuits implicated in the negative control of RAS function as a recurrent theme of RAS‐MAPK signaling upregulation in RASopathies (Bergoug et al., 2020; Brems et al., 2007; Motta et al., 2021; Piotrowski et al., 2014). The gene discussed is SPRED1; the disease is RASopathy.