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Plasma cells (PC) depend on interactions with bone marrow stroma and the resultant growth factors for their long lived survival. Very little is known about the molecular mediators of these survival signals. One such molecule that has recently come of interest is PIM2. PC malignancies such as multiple myeloma (MM) preferentially express PIM2 over its counterparts PIM1 or PIM3 downstream of the PI3K/AKT/mTOR pathway essential for differentiation and survival of PC. In this study, we explored an experimental drug JP_11646 (Jasco Pharmaceuticals LLC) that has a high potency towards PIM kinases, more specifically towards PIM2. Using MM cell lines as a model for long term PC survival, we have shown for the first time that inhibiting PIM2 deregulates survival pathways that involve IL-6, DC protection of MM and CD28 activation by deregulating key survival factors such as NFκB, decreased phosphorylation and inactivation of the PIM2 substrate and pro-apoptotic protein BAD, lower levels of the inactive phosphorylated translational repressor 4EBP1, besides affecting transcription and translation of PIM2 itself. This was recapitulated when PIM2 was silenced with siRNA. Through northerns and protein assays, we also explore the transcriptional and translational dimensions involved in regulating PIM2 in plasma cells. An understanding of the role of PIM2 in MM biology will help to understand how plasma cells survive long term and maintain humoral immunity.