In summary, our data show that the cell polarity protein PALS1 is expressed in lymphocytes and contributes to their optimal activation. Although Dlgh1 and SCRIB were proposed to modulate NF-AT or p38 [9, 10, 17, 18] and NF-AT [7] respectively, a distinct scenario likely occurs for PALS1. Our results support a model in which PALS1 participates to NF-kB activation, upstream of IkBa phosphorylation and degradation. However, how precisely PALS1 modulates NF-kB remains unclear. Because MAGUK function as scaffold units to organize and integrate multi-molecular signaling complexes [13] , it is tempting to speculate that PALS1 nucleates its own signalosome. For example, CARMA1 anchors a .900 kDa complex including the heterodimer BCL10/MALT1 [22] , and Dlgh1 was reported to bind to Lck, Zap70, Wasp [17] , and p38 [10] . In our hands, PALS1 did not integrate the CBM, but its absence reduced CARMA1 binding to BCL10. It will therefore be interesting to identify PALS1 partners in the context of lymphocyte activation. In line with this, CRB3, PATJ and PAR6, which all bound PALS1 to maintain cell polarity [2] , also participate to NF-kB signaling upon TCR ligation in lymphocytes, and might therefore complex with PALS1 in lymphocytes. Altogether, our results strengthen the unexpected function of cell polarity proteins in lymphocyte proliferation [7, 8, 9, 10] , and unveil an original role for PALS1 during TCR-mediated NF-kB activation.