Disease-associated RNA binding protein (RBP) aggregation is a hallmark of several neurodegenerative disorders, contributing to their pathogenesis by disrupting cell homeostasis leading to cell dysfunction. In oculopharyngeal muscular dystrophy (OPMD), an expansion mutation in PABPN1 results in nuclear aggregates, but their role in disease mechanism and cellular dysfunction remains unclear. Using an inducible muscle cell model, we investigated PABPN1's effects on RNA and protein contents in nuclear, cytosolic, and insoluble fractions. We find that PABPN1 aggregates form fibrils similar to those in patients, and PABPN1 function is impaired as in the loss-of-function model. In cells expressing the pathogenic PABPN1, RBPs are enriched in the insoluble fraction, mRNA is sequestered in the nucleus, nuclear export is impaired, and translation efficiency decreases. Additionally, nuclear aggregates lead to reduced endogenous PABPN1 levels. We propose that PABPN1 aggregates and other disease-associated RBPs contribute to PABPN1 gain and loss-of-function, driving cell dysfunction in OPMD.