PDZ and LIM domain protein 5

PDZ and LIM domain protein 5 (PDLIM5) is a scaffolding protein that regulates protein kinase C localization and plays dual roles in cardiac and neuronal development (UniProt: Q96HC4). In cardiomyocytes, it scaffolds PKC to the Z-disk and modulates hypertrophy, while in neurons it contributes to dendritic spine morphogenesis and may restrain postsynaptic growth of excitatory synapses through isoform-specific mechanisms.

PDLIM5 has no curated disease associations listed in UniProt; however, its neuronal functions involving synaptic regulation and spine morphology position it within pathways relevant to neurodegeneration. The protein's ability to influence dendritic structure and synaptic organization connects it to mechanisms implicated in neurodegenerative processes.

PDLIM5 is upregulated in Alzheimer's disease brain tissue. In a human post-mortem AD brain versus age-matched control comparison using TMT-labeled proteomics across four subcellular fractions, PDLIM5 showed increased abundance with a mean log2 fold-change of 0.98 (Chaparral AD proteomics). This elevation may reflect compensatory responses or pathological changes in synaptic structure during AD progression.