The role of protein prenylation in kidney diseases: Molecular basis and therapeutic implications.

Kidney diseases may lead to a life-threatening condition, with their global prevalence increasing day by day. The progressive nature of kidney diseases is driven by a complex interplay of cellular and molecular events, among which protein prenylation plays a pivotal role. Protein prenylation, a lipid-mediated post-translational modification, is essential for the functional regulation of small guanosine triphosphatase binding proteins, including Ras, Rac, Rab, and Rho, which govern cell signaling, proliferation, and membrane dynamics. Aberrant prenylation disrupts these signaling cascades, contributing to podocyte injury, mitochondrial dysfunction, oxidative stress, and renal fibrosis, among others. This review provides an integrated overview of recent advancements in protein prenylation, the effects of these modifications on renal physiology, emerging insights into how altered prenylation drives kidney disease progression and identifies therapeutic strategies targeting this modification. Moreover, we emphasized the potential pharmacological interventions, including bisphosphonates, statins, and others, providing multitargeted therapeutic benefits in various forms of kidney diseases. This review underscores the translational potential of modulating protein prenylation as a novel therapeutic strategy for the management of kidney diseases and for improving clinical outcomes.