In a vicious cycle, the accumulation of lipids in the form of lipid droplets in podocytes, due to altered expression of a variety of genes important in regulating lipid metabolism, leads to mitochondrial dysfunction and inflammation. Vice versa, increased mitochondrial dysfunction and inflammation can directly affect lipid metabolism. This study identifies JAML, a junction adhesion molecule (JAM)-like protein, as an important mediator regulating podocyte lipid metabolism through Sirt1-mediated SREBP1 signaling. ABCA1, ATP-binding cassette subfamily A member 1; ABCG1, ATP-binding cassette subfamily G member 1; ACC1, acetyl-CoA carboxylase alpha; ACO2, aconitase 2; APOE, apolipoprotein E; CD36, cluster of differentiation 36; CPT1, carnitine palmitoyltransferase 1A; FAS, FAS cell surface death receptor; L-FABP, fatty acid-binding protein; IL6, interleukin 6; IL18, interleukin 18; LDLR, low-density lipoprotein receptor; LXR, liver X receptor α; NLRP3, NLR family pyrin-domain-containing 3; PPARα, peroxisome proliferator-activated receptor alpha; PPARδ, peroxisome proliferator-activated receptor delta; SCAP, SREBF chaperone; SCD1, stearoyl-CoA desaturase; SREBP1c, sterol regulatory element-binding transcription factor 1; SREBP2, sterol regulatory element-binding transcription factor 2; SOAT1, sterol O-acyltransferase; TNF, tumor necrosis factor alpha.