Whether it is significant is highly specific to the domain. I think protobuf has accumulated enough problems that every large scale application will eventually

Whether it is significant is highly specific to the domain. I think protobuf has accumulated enough problems that every large scale application will eventually run into a footgun or two. Almost all of them have to do with the generated types, not the wire format. Examples that can noticeably slow things down even for “normal” web apps: map types and deeply nested messages.