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329 Research has found that lysosomal acidity is also within the realm of calcium regulation, where excessive Ca 2+ released from the ER-resident RyR receptor can impair the function of lysosomal V-ATPase, causing lysosomal acidification defects, reducing lysosomal protease activity, and leading to the accumulation of p-tau

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doi: 10.1038/s41467-024-51683-1 151 CloonanSMKimKEstevesPTrianTBarnesPJ

This cascade of metabolic dysregulation not only directly induces the phenotype switching of PASMCs from a contractile to a highly proliferative and migratory synthetic phenotype [132] but also causes significant medial wall thickening, ultimately driving PH disease progression