In addition, the human SEL-11 ortholog, Synoviolin, is essential for development in mice and has been implicated in hyperproliferation of synovial tissues in rheumatoid arthritis and in the degradation of p53 and IRE1 [26], [27], [28]; furthermore, there appears to be multiple modes of crosstalk between Notch and p53 [29]. This evidence concerns the gene ERN1 and rheumatoid arthritis.