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Despite limited sequence homology to cellular kinases such as Akt or PKA, US3 phosphorylates diverse substrates to manipulate multiple pathways. This review summarizes current knowledge of US3 functions across several major areas, including suppression of innate immune responses through modulation of NF\u2010\u03baB, ERK\/MAPK, TBK1\/IRF3, RIG\u2010I; promotion of cell survival via phosphorylation of canonical Akt substrates such as TSC2, FOXO1\/3, and BAD; and facilitation of nuclear egress through modification of lamin A\/C, emerin, and the nuclear egress complex proteins UL31 and UL34. By comparing US3's strategies with those of cellular kinases and other viral effectors, this review highlights convergent mechanisms of host manipulation. 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