Myosin regulatory light chain interacting protein (MYLIP)

Myosin regulatory light chain interacting protein (MYLIP), also known as IDOL (inducible degrader of the LDL receptor), is a human E3 ubiquitin-protein ligase responsible for the ubiquitination and lysosomal degradation of the low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), and apolipoprotein E receptor 2 (ApoER2)[1][2][4][5]. By targeting these receptors, MYLIP regulates cellular cholesterol uptake and plays a key role in cholesterol homeostasis. Its expression is transcriptionally controlled by liver X receptor (LXR) in response to intracellular sterol levels. MYLIP is also an ERM-like cytoskeletal protein that inhibits neurite outgrowth by mediating the degradation of myosin regulatory light chain. Therapeutically, MYLIP is being investigated as a target in hypercholesterolemia and atherosclerosis: inhibition of MYLIP/IDOL is hypothesized to increase LDL receptor density and lower plasma LDL cholesterol[2][8]. Genetic and animal studies suggest important roles in lipid metabolism, energy homeostasis, and neuronal signaling. There are currently no clinically approved drugs targeting MYLIP, but the pathway is of significant research interest for cardiovascular and neurological disease[2][4][5].

Other names

Inducible degrader of the LDL receptor (IDOL)E3 ubiquitin-protein ligase MYLIPModulator of immune recognition (MIR)Band 4.1 superfamily member BZF1E3 ubiquitin ligase-inducible degrader of the low density lipoprotein receptorRING-type E3 ubiquitin transferase MYLIPCellular modulator of immune recognition (c-MIR)9430057C20RikLOC107986517

E3 ligase inhibition (blocks MYLIP-mediated ubiquitination and degradation of LDL receptor, increasing LDL receptor density and lowering plasma LDL cholesterol)[2][4]; Modulation of cholesterol homeostasis (by influencing LDLR, VLDLR, ApoER2 receptor stability)[2].