Male infertility is common during advanced age. Although mechanisms underlying age-related infertility are complex and currently incompletely understood, a feature of testicular ageing is decreased cell numbers within the functional unit of the testes, the seminiferous tubule. Five years ago, a pro-inflammatory form of cell death called ‘necroptosis’ that relies upon a protein called MLKL has been proposed as a mechanism to explain age-related male infertility through mouse studies (Li. D et al., 2017). Accordingly, we tested whether the mouse testis is indeed capable of undergoing necroptosis by injecting the pro-necroptotic agent, TNF + smac-mimetic Compound A + z-VAD-fmk (TSZ) directly into the testes of Mlkl+/+ and Mlkl-/-littermate mice. Blinded quantification showed that in 3 days, intra-testicular injection of TSZ significantly reduced cell numbers within seminiferous tubules of Mlkl+/+ but not Mlkl-/- mice (p=0.003). Unexpectedly, through immunofluorescence studies in untreated Mlkl+/+ mice testes, it appears that the cells capable of necroptosis (i.e. MLKL-expressing cells) are located in the interstitium rather than within seminiferous tubules. Thus, which testicular cell type undergoes necroptosis, and whether this contributes to age-related male infertility remain open questions. We are now: 1) identifying the specific cells inside the interstitium of testes that undergo necroptosis via immunohistochemistry and immunofluorescence, 2) quantifying necroptotic changes in the major supportive cells that are important for sperm production, and 3) pinpointing where necroptosis occurs over time in testes of live mice using intra-vital imaging. We expect these studies will not only provide the first real-time footage of necroptotic cell death in vivo, but also redefine the role of MLKL in testicular degeneration and ageing.