SMPDL3B and Insulin resistance: 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.