ABSTRACT The dual‐specificity tyrosine‐regulated kinase (DYRK) family, a conserved serine/threonine kinase group, plays a pivotal role in the regulation of metabolic homeostasis by modulating glucose/lipid metabolism, oxidative stress, and calcium‐phosphorus balance. Mammalian DYRKs are classified into Class I (DYRK1A and DYRK1B) and Class II (DYRK2, DYRK3, and DYRK4) based on their structural differences, tissue‐specific expression, and functional diversity in maintaining systemic metabolic balance. Dysregulation of DYRK‐mediated metabolic homeostasis drives the progression of metabolic kidney diseases, key complications of chronic kidney disease. Specifically, DYRK1A aggravates diabetic nephropathy and renal fibrosis; DYRK1B mutations directly trigger mTORC2‐mediated lipotoxicity and insulin resistance, promoting glomerulosclerosis; DYRK2 disrupts calcium‐phosphorus metabolism and aggravates renal vascular calcification via the Notch/Wnt pathway. DYRK‐targeted inhibitors, including harmine, AZ191, and curcumin, have shown therapeutic potential in promoting β‐cell regeneration, alleviating metabolic disorders, and suppressing fibrosis. However, insufficient tissue targeting and off‐target risks remain critical bottlenecks for clinical translation. Future efforts should integrate gene editing with kidney‐specific delivery technologies to enhance therapeutic precision. This review systematically summarizes the structural and functional bases of the DYRK family, its regulatory role in metabolic homeostasis, and its therapeutic prospects in related renal diseases, providing new strategies for precise intervention.
Zhu et al. (Sun,) studied this question.