Reversible protein phosphorylation is a significant regulatory mechanism in many cellular functions, such as the dephosphorylation of Serine/Threonine protein residues catalyzed by protein phosphatase. In this study, the full-length STPP1-α gene from Penaeus monodon was cloned, characterized, and analyzed for its constitutive expression in WSSV-negative P. monodon organs. The gene was originally an isotig isolated from the gills of P. monodon that survived WSSV infection. PmSTPP1-α gene (GenBank: KX385833) has a total of 2,171 bp, with a 990 open reading frame (ORF) that encodes 329 amino acids (aa), sharing a 93% sequence identity with human Serine/Threonine PP1-α catalytic subunit. The protein has a single conserved catalytic domain and shares almost all the conserved sites and functional residues of the human protein phosphatase, which particularly might have putative functions to viral protein synthesis. Using clustering analysis, PmSTPP1-α was verified to be the –α isoform while the reported L. vannamei STPP1 is the β form. In silico homology modelling predicts similar structures for PmSTPP1-α and STPP1 from H. sapiens. Conserved functional domains for metal binding, target protein interaction, and toxin binding sites were identical in sequence and predicted structure. The observed variations in amino acid sequence were outside these conserved domains but should be further studied to determine their potential effects on function. Current molecular docking predictions for PmSTPP1-α against three proteins from known P. monodon pathogens suggest specific functional interactions with the target protein binding domain and the molecular toxin interaction sites. PmSTPP1-α was found to be ubiquitously and highly expressed in organs of WSSV-negative P. monodon, further investigations on the interactions of this protein will help validate its predicted involvement in the P. monodon immune response.