Understanding　generic　mechanisms　of　functions　shared　by　the　secretory　phospholipase　A2　(sPLA2)　family　involved　in　the　lipid　metabolism　and　cell　signaling　and　the　molecular　basis　of　function　specificity　for　family　members　is　an　intriguing　but　challenging　problem　for　biologists.　Here,　we　explore　the　issue　through　extensive　analyses　using　a　combination　of　structure-based　methods　and　bioinformatics　tools　on130　sPLA2　family　members.　The　principal　component　analysis　of　the　structure　ensemble　reveals　that　the　enzyme　has　an　open-close　motion　which　helps　widen　the　substrate　binding　channel,　facilitating　its　binding　to　phospholipid.　Performing　elastic　network　model　and　sequence　analyses　found　that　the　residues　critical　for　family　functions,　such　as　cysteine　and　catalytic　residues,　are　highly　conserved　and　undergo　minimal　movements,　which　is　evolutionarily　essential　as　their　perturbation　would　impact　the　function,　while　the　four　residue　regions　involved　in　the　association　with　the　calcium　ion/membrane　are　lowly　conserved　and　of　high　mobility　and　large　variations　in　low-to-intermediate　frequency　modes,　which　reflects　the　specificity　of　members.　The　analyses　from　perturbation　response　scanning　also　reveal　that　the　above　four　regions　with　high　sensitivity　to　an　external　perturbation　are　member-specific,　suggesting　their　different　roles　in　allosteric　modulation,　while　the　minimal　sensitive　residues　are　the　shared　characteristics　across　family　members,　which　play　an　important　role　in　maintaining　structural　stability　as　the　folding　core.　This　study　is　helpful　for　understanding　how　sequences,　structures,　and　dynamics　of　sPLA2　family　members　evolve　to　ensure　their　common　and　specific　functions　and　can　provide　a　guide　for　accurate　design　of　proteins　with　finely　tuned　activities.