Even though the exact functional consequences of this feature remain elusive, several previous observations underline the importance of this amino-terminal element: (i) at the far-amino-terminus is an IAP-interacting motif through which supposedly HtrA2 function can be over-activated upon IAP-binding43,44, (ii) the amino-terminus together with helix α1 are involved in inter-subunit communication and therefore important for the positive cooperativity of HtrA216,30, (iii) some Parkinson’s disease associated mutations as well as a putative phosphorylation site reside within this helix63,64. This evidence concerns the gene HTRA2 and Parkinson disease.