Poldip2 by itself or via interaction with its binding partners is involved in multiple signaling pathways, modulating focal adhesion turnover, ECM regulation, cell migration, proliferation and differentiation, renal sensory-nerve activation, DNA replication and damage repair, mitochondrial function and morphology and autophagy. Those processes contribute to vascular stiffness, collateral formation, myocardium remodeling, the diuretic/natriuretic response, BBB permeability and retinal degeneration. BBB, blood-brain-barrier; PCNA, proliferating cell nuclear antigen; MMPs, matrix metalloproteinases.