Notably, we demonstrate that viral infection suppresses PBLD transcription via downregulation of transcription factor EB (TFEB) and promotes PBLD protein degradation through upregulation of the membrane‐associated RING finger protein 2 (MARCH2)‐mediated ubiquitin‐proteasomal pathway, thereby facilitating viral immune evasion and enhancing viral replication. Here, PBLD is linked to viral infectious disease.