Several studies reported functional down-regulation of the anti-apoptotic protein BCL-xL as a consequence of phosphorylation or deamidation of amino acids within its large intrinsically disordered loop. We meant to elucidate these poorly understood mechanisms of apoptotic regulation, and at the same time develop a case study of functional interplay between folded and disordered segments within the same protein. We present here preliminary results towards a structural and mechanistic understanding of these phenomena. Our studies suggest that the post translational modification of its intrinsically disordered loop may trigger conformational rearrangements in the folded core of BCL-xL that decrease its affinity for BH3-only protein partners.