HCFC1R1 (host cell factor C1 regulator 1) functions as a regulator of HCFC1 (HCF-1) subcellular localization and activity. HCFC1R1 contains a functional HCF-binding motif and a leucine-rich nuclear export sequence, allowing it to shuttle between nucleus and cytoplasm in a CRM1-dependent manner 1. Overexpression of HCFC1R1 promotes accumulation of HCF-1 in the cytoplasm through CRM1-mediated nuclear export 1. This cytoplasmic pool of HCF-1 is functionally important for herpes simplex virus (HSV) infection, as HCFC1R1-mediated export may facilitate the nuclear import of virion-derived VP16 protein, which requires cytoplasmic HCF-1 binding to activate viral immediate-early gene transcription 1. In uninfected cells, HCF-1 functions as a coactivator for cellular transcription factors and plays essential roles in cell proliferation 1. By modulating HCF-1 localization, HCFC1R1 regulates both normal cellular functions and viral replication strategies. The regulation of HCFC1R1-mediated HCF-1 export represents an important mechanism controlling transcriptional activity and viral-host cell interactions.