The lipid transfer protein AZI1 is required for the priming of various systemic defense responses including: SAR (systemic acquired resistance); ISR (induced systemic resistance); and the uptake and mobilization of azelaic acid (AZA). Generated from the oxidation of plastid lipids during infections, AZA primes systemic defenses when applied to leaves or roots and induces striking changes in root development. These changes require the development- and defense-associated kinase MPK3, which is also required for SAR, ISR, and sensitivity to AZA. The AZI1 family also influences root development during salt stress and in response to AZA treatment similar to MPK3, which suggests the AZI1 protein family may serve as downstream coordinators of MPK3-dependent development and stress responses. Furthermore, MPK3 promotes the accumulation of AZI1 at plastids during infections, which suggests a critical role for AZI1’s plastid association in defense signaling. AZI1 is highly dynamic and traffics along the contact sites among the plastid, ER, and plasma membranes. Unlike canonical “signal anchored” proteins that target plastid membranes, AZI1’s normal pattern of plastid association requires a bipartite targeting signal that consists of a N-terminal hydrophobic domain and an internal proline-rich region. Including AZI1, the AZI1 gene family consists of seven short genes tandemly aligned on chromosome 4. Except for AZI5/AZI6 and AZI7, which have a shortened or absent PRR, respectively, AZI1 family proteins show a similar localization pattern as AZI1 and contribute to the priming of systemic immunity.