VP16 is a component of virion tegument layer that is required for the transcription of the viral immediate-early (IE) genes. In case of human herpes simplex virus (HSV) infection, VP16 binds to HCF-1 (host cell factor 1) and translocates to the nucleus to form a complex with the POU domain protein Oct-1. This complex then directs high level IE gene transcription by the potent activation domain in the C terminus of VP16. HCF-1 provides two functions required by VP16, complex assembly and nuclear targeting []. This entry represents HPIP (HCF-1 β-propeller-interacting protein), also known as host cell factor C1 regulator 1 (HCFC1R1), which is a small cellular polypeptide that binds to the β-propeller domain of HCF-1. HPIP regulates HCF-1 activity by modulating its subcellular localisation. HPIP-mediated export may provide the pool of cytoplasmic HCF-1 required for import of VP16 into the nucleus [].