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Clinical trials have consistently demonstrated that gastrointestinal adverse effects are most common during the first 48 weeks of therapy and typically diminish as physiological adaptation occurs

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Turk J Gastroenterol

Ion transport mechanisms, including the plasma membrane Ca 2+ ATPase (PMCA) and anion exchanger 1 (AE1, Band 3), also function as checkpoints: PMCA extrudes excess Ca 2+ to limit overload, with its activity modulated by ceramide or AA, while AE1 mutations disrupting ion balance promote eryptosis (Nicolay et al., 2008