Targeting the untargeted: Molecular insights and emerging therapeutic strategies for primary aldosteronism.

Primary aldosteronism (PA), the most common form of endocrine hypertension, is evolving from a simple hormonal disorder to a complex molecular syndrome. While somatic mutations in genes like KCNJ5 and CACNA1D illuminate part of the pathogenesis, the integrated role of epigenetic dysregulation remains a critical frontier. This review argues that the traditional "one-size-fits-all" approach, reliant on conventional mineralocorticoid receptor antagonists (MCRAs), is inadequate due to its off-target effects and failure to address residual cardiovascular risk. We comprehensively synthesize emerging evidence that the future of PA management lies in molecular subtyping. This paradigm shift is already being catalyzed by next-generation agents-including non-steroidal MCRAs and aldosterone synthase inhibitors(ASIs), which promise targeted intervention. By critically appraising the path from molecular mechanisms to precision therapeutic strategies, this review delineates a roadmap for overcoming the current dissociation between hypertension control and long-term organ protection, ultimately paving the way for a personalized medicine era in PA.