Yes, wouldn't even consider using node without TypeScript, personally.
Really, the main pieces that could seems a little mysterious are type definitions and compiler options. tsconfig.json exists in the root of the project for compiler options. Type definitions can be managed by a library called 'typings', or for TypeScript 2.0, type definitions can be managed with npm.
The biggest problems I had with TypeScript involved type definitions, combined with the module system. Now, the latter is not TS' fault and a bit clusterfuck at the moment for everyone, but it's a bit more complicated if you add TS to the mix.
It's improved immensely though in the past months/year.
Really, the main pieces that could seems a little mysterious are type definitions and compiler options. tsconfig.json exists in the root of the project for compiler options. Type definitions can be managed by a library called 'typings', or for TypeScript 2.0, type definitions can be managed with npm.