PPL and eosinophilic esophagitis: Additionally, we demonstrate the potential loss of RhoGTPase activity as a consequence of these variants and that this process may contribute to EoE even in patients without primary genetic variants in DSP and PPL. These findings underscore a pathogenic role for desmosomal dysfunction in EoE and the likely intersection of this with CAPN14– and RhoGTPase–mediated pathways.