Among signaling complexes located in raft domains that are heavily dependent on the PM lipid composition, we are focused on the insulin receptor (IR)-signaling complex for several reasons: (1) IR signaling is a key modulator of podocyte function10–12; (2) SMPDL3b is strongly upregulated in glomeruli of patients with insulin resistance and diabetic kidney disease (DKD)3; (3) IR exists in two isoforms which are characterized by distinct affinities for lipid raft domains13 and which are differentially expressed in various cell types suggesting distinct functions. The gene discussed is INSR; the disease is Insulin resistance.