Introduction: Salt-inducible kinases (SIKs), members of the AMP-activated protein kinase (AMPK) family, are essential regulators of cellular signaling. These kinases target critical substrates, including histone deacetylases (HDACs) and CREB-regulated transcriptional coactivators (CRTCs), to modulate diverse biological processes such as metabolism, proliferation, inflammation, and apoptosis. Growing evidence indicates that SIK dysregulation is associated with several diseases, including epilepsy, metabolic syndromes, lung cancer, and systemic hypertension. Methods: Relevant literature was sourced from PubMed, Scopus, and Google Scholar using keywords such as salt-inducible kinase, pulmonary arterial hypertension, YAP pathway, hypertrophy, and vascular remodeling. Over 130 articles were meticulously analyzed to compose this review.Methods Results: This review highlights the role of SIKs in pulmonary arterial hypertension (PAH), although this research area remains underexplored. SIKs regulate pathways that influence inflammation and metabolic reprogramming in PAH, and their inhibition has the potential to mitigate endothelial dysfunction and vascular remodeling. Discussion: The review focuses on the involvement of SIKs in the pathophysiology of PAH and their potential as therapeutic targets. Conclusion: SIKs play a critical role in the pathogenesis of PAH by mediating inflammation and vascular remodeling. We outline the molecular pathways through which SIK activity influences key cellular processes relevant to PAH, highlighting their potential as promising therapeutic targets.
Kaushik et al. (2026) studied this question.