Plays essential roles in viral nuclear egress to mediate capsid transit across the nuclear membrane and also in the inhibition of host immune response. Facilitates nuclear egress cooperatively with host C1QBP and protein kinase C/PKC to induce lamin A/C phosphorylation and subsequent reorganization. In turn, lamina disassembles and nuclear egress occurs. Recruits the serine/threonine protein phosphatase PPP1CA/PP1-alpha to dephosphorylate the translation initiation factor eIF-2A, thereby couteracting the host shutoff of protein synthesis involving double-stranded RNA-dependent protein kinase EIF2AK2/PKR. In turn, controls host IRF3 activation and subsequently inhibits host interferon response. Controls the DNA sensing pathway by interacting with and inhibiting host STING/TMEM173. Also down-modulates the host MHC class II proteins cell surface expression. Acts as a neurovirulence factor that has a profound effect on the growth of the virus in central nervous system tissue, by interqcting with host BECN1 and thereby antagonizing the host autophagy response. Interacts with human PPP1CA to form a high-molecular-weight complex that dephosphorylates eIF2-alpha (PubMed:9023344, PubMed:9694816, PubMed:15705855). Binds to proliferating cell nuclear antigen (PCNA), which may release host cells from growth arrest and facilitate viral replication (PubMed:12907392). Interacts (via N-terminus) with host C1QBP and PRKCA. Interacts with protein UL31. Interacts with host TBK1. Interacts with host STING/TMEM173; this interaction inhibits the intracellular DNA sensing pathway. Interacts with host BECN1; this interaction modulates host autophagy (By similarity). At early times in infection, colocalizes with PCNA and replication proteins in the host cell nucleus, before accumulating in the host cytoplasm by 8 to 12 hours post-infection. The triplet repeats region may play a role in modulating virus egress. ICP34.5 is detected as early as 3 hpi prior to viral replication but reaches maximal levels late in infection. ICP34.5 gene is therefore classified as gamma-1 or leaky late gene (By similarity). The phosphatase activity of the ICP34.5-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, which inhibits viral replication. Belongs to the PPP1R15 family.