The adaptor PALS1 is crucial for cellular architecture as it maintains the apico-basal polarity in epithelial cells and authorizes indirect interactions between CRB and PATJ [11, 12] . Interestingly, Dlgh1 and PALS1 share a COOH-terminal part composed of a PSD-95/Dlg/ZO-1 (PDZ) domain followed by an SH3 domain adjacent to an inactive Guanylate kinase (GK) homology region [2] . This unique sequence of PDZ/SH3/GK defines the so-called membrane-associated guanylate kinase (MAGUK) proteins family, a group of molecules that serve as scaffolds to organize multi-protein signalosomes through their protein-protein interaction domains [13] . For example, the MAGUK-containing CARMA1 emerges as a central regulator of lymphocytes activation and proliferation downstream of antigen receptor stimulation [14] . Indeed, CARMA1 operates as scaffold to recruit the heterodimer BCL10/ MALT1 (CBM complex), a key step for conveying NF-kB signaling [14, 15, 16] . In addition to its established role in polarity, Dlgh1 was shown to modulate lymphocyte proliferation upon T-cell receptor ligation, possibly through p38 recruitment or via the transcription factor NF-AT [9, 10, 17, 18] .