Interleukin-35 (IL35) binding activates the IL35 receptor complex and facilitates Tyrosine-protein kinase JAK (JAK) phosphorylation. Subsequently, Signal transducer and activator of transcription 1-alpha/beta (STAT1) and STAT4 bind to the receptor complex and are activated by tyrosine phosphorylation (Collison et al. 2012). Although it is known that JAKs are involved in STATs phosphorylation (Stark GR and Darnell JE, 2012), it is not clear how other components of the IL35 receptor complex contribute to STAT1/STAT4 phosphorylation. For this reason, this event is assigned a black box status.