However, other processes are described in order to provide alternative explanations for Ca2+ dysregulation in B-CLL cells such as a BCR autonomous signaling capacity due to an internal epitope present in the second framework of stereotyped IgHV that can be abrogated by using a BCR signaling inhibitor [15], an incapacity of the ER to release Ca2+ due to an inhibitory interaction between Bcl-2 (overexpressed in B-CLL cells) and the endoplasmic InsP3R [16], and last but not least an incompletely characterized BCR independent Ca2+ pathway recently described in B-CLL cells [17, 18]. The gene discussed is BCL2; the disease is B-cell chronic lymphocytic leukemia.