Pdlim5, also known as ENH (Enigma homolog), is a cytoskeleton-related cytoplasmic protein with a molecular mass of about 63 KDa, consisting of a PDZ domain at the N-terminus and three LIM domains at the C-terminus. It binds to the cytoskeleton and membrane proteins via its PDZ domain and interacts with signaling molecules through its LIM domain. PDLIM5 plays important roles in regulating cell proliferation, differentiation, and cell fate decision in multiple tissues and cell types, and is involved in pathways like p38-MAPK [1,3].

In chicken skeletal muscle satellite cells, knocking down PDLIM5 impacts the MAPK signaling pathway, and it has been shown that PDLIM5 promotes cell proliferation and differentiation by activating the p38-MAPK signaling pathway, suggesting its involvement in chicken skeletal muscle growth and development [3]. In rat primary hippocampal neurons, knockdown of Pdlim5 reduces dendrite branching, indicating its role in neuronal dendrite morphology [2,8].

In lung cancer cells, knockdown of PDLIM5 decreases cell migration and invasion, and it has been found that PDLIM5 inhibits STUB1-mediated degradation of SMAD3 to promote these processes [5]. In prenatal stress offspring rats, PDLIM5 can improve depression-like behavior, and methylation of its promoter is observed in male but not female rats [4].

In pigs, PDLIM5-short, a spliceosome, suppresses myoblast proliferation and differentiation [6]. In neurons, knockdown of PDLIM5 rescues the neuron from PMA-induced growth cone collapse [7]. In SH-SY5Y cells, knocking down PDLIM5 abolishes nicotine-induced upregulation of α7nAChRs [9]. In human kidney, depletion of PDLIM5 reduces kidney anion exchanger 1 (kAE1) at the cell membrane [10].

In conclusion, Pdlim5 is crucial for various biological processes including muscle development, neuronal morphology, and cell migration. Its role in diseases such as depression and lung cancer has been revealed through model-based research, which provides valuable insights into understanding these disease mechanisms and potentially developing new treatment strategies.