The Role of HILPDA in Diseases: Mechanisms and Functional Insights.

Hypoxia-inducible lipid droplet-associated protein (HILPDA) has emerged as a critical regulator of lipid metabolism, attracting considerable attention across diverse biomedical fields. HILPDA modulates cellular energy homeostasis primarily through its influence on lipid droplet (LD) formation. By inhibiting adipose triglyceride lipase (ATGL) to suppress triacylglycerol (TAG) hydrolysis and activating diacylglycerol acyltransferase 1 (DGAT1) to promote TAG synthesis, HILPDA serves as an indispensable regulatory hub of lipid homeostasis. Despite growing evidence underscoring its multifaceted roles, a comprehensive understanding of HILPDA's molecular characteristics, regulatory mechanisms, and disease associations remains incomplete. This review systematically summarizes current knowledge on HILPDA, focusing on its molecular properties and regulatory pathways, and explores its functional significance in neoplastic and non-neoplastic diseases. By integrating recent research advances, this review aims to provide a theoretical foundation and strategic guidance for future basic and clinical investigations of HILPDA.