Current evidence implicates three primary mechanisms of proteostasis impairment in the progression of atrial remodeling and AF development, including impaired protein quality control (PQC) system, histone deacetylase 6 (HDAC6)-induced disruption of the microtubule network, and DNA damage-induced PARP-1 activation with subsequent depletion of NAD + levels in mitochondria. Here, HDAC6 is linked to atrial fibrillation.